Details for: ADAMTS3

Gene ID: 9508

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: ADAMTS3

Ensembl ID: ENSG00000156140

Description: ADAM metallopeptidase with thrombospondin type 1 motif 3

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • retinal cone cell CL0000573
    CSI 7.33
    rCSI 11.8%
    PRS 93.11
  • pulmonary alveolar type 2 cell CL0002063
    CSI 6.27
    rCSI 9.73%
    PRS 97.17
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 6.25
    rCSI 15.18%
    PRS 90.57
  • GABAergic neuron CL0000617
    CSI 5.8
    rCSI 19.42%
    PRS 89.67
  • ependymal cell CL0000065
    CSI 5.61
    rCSI 11.39%
    PRS 87.63
  • glioblast CL0000030
    CSI 5.15
    rCSI 8.21%
    PRS 93.55
  • retinal rod cell CL0000604
    CSI 4.88
    rCSI 8.6%
    PRS 94.84
  • S cone cell CL0003050
    CSI 4.68
    rCSI 20.55%
    PRS 94.38
  • blood vessel endothelial cell CL0000071
    CSI 4.25
    rCSI 8.82%
    PRS 96.5
  • fibroblast of lung CL0002553
    CSI 4.09
    rCSI 3.81%
    PRS 98.23
  • hepatic stellate cell CL0000632
    CSI 4.06
    rCSI 15.22%
    PRS 95.99
  • parietal epithelial cell CL1000452
    CSI 3.79
    rCSI 10.13%
    PRS 95.36
  • kidney connecting tubule epithelial cell CL1000768
    CSI 3.68
    rCSI 9.32%
    PRS 94.95
  • alveolar type 1 fibroblast cell CL4028004
    CSI 3.15
    rCSI 3.45%
    PRS 98.11
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.96
    rCSI 4.2%
    PRS 96.48
  • chondrocyte CL0000138
    CSI 2.89
    rCSI 4.6%
    PRS 95.24
  • inhibitory interneuron CL0000498
    CSI 2.79
    rCSI 6.44%
    PRS 92.92
  • renal principal cell CL0005009
    CSI 2.7
    rCSI 7.02%
    PRS 96.88
  • glutamatergic neuron CL0000679
    CSI 2.42
    rCSI 4.98%
    PRS 90.16
  • regular atrial cardiac myocyte CL0002129
    CSI 2.4
    rCSI 7.73%
    PRS 94.82
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 2.35
    rCSI 5.11%
    PRS 90.31
  • retinal blood vessel endothelial cell CL0002585
    CSI 2.18
    rCSI 3.48%
    PRS 98.15
  • amacrine cell CL0000561
    CSI 2.03
    rCSI 5.88%
    PRS 93.04
  • mesothelial cell CL0000077
    CSI 1.86
    rCSI 7.28%
    PRS 89.89
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 1.76
    rCSI 5.79%
    PRS 90.69
  • GABAergic amacrine cell CL4030027
    CSI 1.68
    rCSI 5.74%
    PRS 90.03
  • basophil CL0000767
    CSI 1.64
    rCSI 3.47%
    PRS 98.24
  • medium spiny neuron CL1001474
    CSI 1.45
    rCSI 12.52%
    PRS 92.96
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 1.4
    rCSI 3.34%
    PRS 91.63
  • direct pathway medium spiny neuron CL4023026
    CSI 1.39
    rCSI 33.21%
    PRS 89.8
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.37
    rCSI 33.1%
    PRS 89.54
  • dopaminergic neuron CL0000700
    CSI 1.23
    rCSI 6.96%
    PRS 91.44
  • retinal ganglion cell CL0000740
    CSI 1.18
    rCSI 2.6%
    PRS 92.19
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.93
    rCSI 2.91%
    PRS 93.38
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.68
    rCSI 3.98%
    PRS 91.99

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [ADAMTS3](/details-gene/9508) (A Disintegrin and Metallopeptidase with Thrombospondin type 1 motif 3) is a protein-coding gene located on chromosome 4q13.3. It encodes a member of the ADAMTS family of zinc-dependent proteases that play crucial roles in extracellular matrix (ECM) remodeling. The primary function of [ADAMTS3](/details-gene/9508) is the processing of procollagens, specifically cleaving the N-propeptide from procollagen types I, II, and III, a critical step in the formation of mature collagen fibrils ([Link](https://doi.org/10.1074/jbc.m103466200)). Consistent with this role, the gene shows significant expression in a diverse range of cell types involved in structural maintenance and specialized ECM environments, including various neurons, retinal cells, and fibroblasts. Clinically, loss-of-function mutations in [ADAMTS3](/details-gene/9508) are known to cause Hennekam lymphangiectasia-lymphedema syndrome 3, highlighting its essential role in lymphatic development and function ([Link](https://doi.org/10.1093/hmg/ddx297)). ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [ADAMTS3](/details-gene/9508) indicates its importance in tissues with highly specialized or actively maintained extracellular matrices. The gene exhibits its most significant expression in several distinct cellular contexts: * **Neural and Sensory Tissues:** The highest cell significance index (CSI) is observed in [retinal cone cell](/details-cell/CL0000573) (CSI: 7.33), with strong signals also present in [L2/3-6 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4023040) (CSI: 6.25), [GABAergic neuron](/details-cell/CL0000617) (CSI: 5.80), and [retinal rod cell](/details-cell/CL0000604) (CSI: 4.88). This pattern suggests a critical role for [ADAMTS3](/details-gene/9508) in the formation and maintenance of the unique ECM environments of the retina and central nervous system, which are essential for neuronal function and structural integrity. * **Epithelial and Fibroblastic Cells:** High significance is also noted in various structural and barrier cells, including [pulmonary alveolar type 2 cell](/details-cell/CL0002063) (CSI: 6.27), [ependymal cell](/details-cell/CL0000065) (CSI: 5.61), [blood vessel endothelial cell](/details-cell/CL0000071) (CSI: 4.25), [fibroblast of lung](/details-cell/CL0002553) (CSI: 4.09), and [hepatic stellate cell](/details-cell/CL0000632) (CSI: 4.06). This widespread expression in cells responsible for producing and organizing connective tissue aligns directly with its fundamental function in collagen biosynthesis. * **Pathological Context:** Notably, [ADAMTS3](/details-gene/9508) shows a high CSI in [glioblast](/details-cell/CL0000030) (CSI: 5.15), a type of malignant brain tumor. This suggests that its ECM-remodeling capabilities may be co-opted by cancer cells to facilitate tumor growth and invasion. ## Pathways and Molecular Function The functional annotations for [ADAMTS3](/details-gene/9508) strongly corroborate its role as an extracellular protease involved in collagen maturation. Its molecular functions are dominated by [metalloendopeptidase activity](/details-go/GO:0004222) and [zinc ion binding](/details-go/GO:0008270), characteristic of this enzyme class. Biologically, it is a key participant in processes such as [collagen catabolic process](/details-go/GO:0030574), [collagen fibril organization](/details-go/GO:0030199), and the broader [extracellular matrix organization](/details-go/GO:0030198). This is further detailed in the Reactome pathways, which place [ADAMTS3](/details-gene/9508) as a central enzyme in [Collagen biosynthesis and modifying enzymes](/details-pathway/R-HSA-1650814) and [Collagen formation](/details-pathway/R-HSA-1474290). Its localization to the [extracellular space](/details-go/GO:0005615) and [collagen-containing extracellular matrix](/details-go/GO:0062023) is consistent with its function in processing secreted procollagens. The involvement in the [positive regulation of vascular endothelial growth factor signaling pathway](/details-go/GO:1900748) suggests a secondary role in angiogenesis, which may be relevant in both development and disease. ## Research Directions The expression profile and functional annotation of [ADAMTS3](/details-gene/9508) point toward several compelling areas for future investigation, particularly concerning its roles in cancer and specialized tissue maintenance. **Proposed Hypotheses:** 1. Given its high expression in [glioblast](/details-cell/CL0000030) and its established role in ECM remodeling, [ADAMTS3](/details-gene/9508) may be a critical facilitator of glioblastoma invasion. Upregulation of [ADAMTS3](/details-gene/9508) in tumor cells could enable them to degrade the surrounding brain matrix, promoting infiltration into healthy tissue. 2. The prominent expression of [ADAMTS3](/details-gene/9508) in diverse retinal cell types, such as [retinal cone cell](/details-cell/CL0000573) and [retinal rod cell](/details-cell/CL0000604), suggests it is essential for maintaining the highly organized interphotoreceptor matrix. Its dysregulation could contribute to the pathology of retinal degenerative diseases characterized by ECM abnormalities. 3. In the lung, the high expression in both [pulmonary alveolar type 2 cell](/details-cell/CL0002063) and [fibroblast of lung](/details-cell/CL0002553) points to a potential role in lung homeostasis and pathology. Over-activity of [ADAMTS3](/details-gene/9508) could contribute to the excessive collagen deposition seen in idiopathic pulmonary fibrosis. **Suggested Experimental Approach:** To test the hypothesis that [ADAMTS3](/details-gene/9508) drives glioblastoma invasion (Hypothesis 1), a targeted experiment could be performed. Using CRISPR-Cas9 or shRNA to stably knock down [ADAMTS3](/details-gene/9508) expression in a highly invasive glioblastoma cell line (e.g., U-87 MG or patient-derived xenografts). The invasive capacity of these knockdown cells could then be compared to control cells using a three-dimensional organotypic brain slice culture or a transwell Matrigel invasion assay. A significant reduction in the distance and number of invading knockdown cells would provide direct evidence for the role of [ADAMTS3](/details-gene/9508) in mediating glioblastoma invasion. **Therapeutic Potential:** As an extracellular and secreted enzyme, [ADAMTS3](/details-gene/9508) represents an accessible therapeutic target. Its potential role in promoting glioblastoma invasion makes it a candidate for **inhibition**. The development of highly specific small molecule inhibitors or neutralizing monoclonal antibodies that block the catalytic domain of [ADAMTS3](/details-gene/9508) could be a viable strategy to suppress tumor progression and metastasis. Such a therapeutic would have the advantage of targeting a process central to cancer cell dissemination, potentially in combination with standard cytotoxic therapies.

Genular Protein ID: 3918105852

Symbol: ATS3_HUMAN

Name: A disintegrin and metalloproteinase with thrombospondin motifs 3

UniProtKB Accession Codes:

O15072 A1L3U9 Q9BXZ8

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 4 ChiTaRS 1 DNASU 1 DisGeNET 1 EC 1 EMBL 7 Ensembl 1 GO 17 Gene3D 4 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 11 KEGG 1 MANE-Select 1 MEROPS 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 7 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 3 RefSeq 1 SMART 1 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 11408482

Title: Procollagen II amino propeptide processing by ADAMTS-3. Insights on dermatosparaxis.

PubMed ID: 11408482

DOI: 10.1074/jbc.m103466200

PubMed ID: 9205841

Title: Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.

PubMed ID: 9205841

DOI: 10.1093/dnares/4.2.141

PubMed ID: 28985353

Title: Loss of ADAMTS3 activity causes Hennekam lymphangiectasia-lymphedema syndrome 3.

PubMed ID: 28985353

DOI: 10.1093/hmg/ddx297

Sequence Information:

  • Length: 1205
  • Mass: 135603
  • Checksum: 01FA661B1C6BFF1B
  • Sequence:
    • MVLLSLWLIA AALVEVRTSA DGQAGNEEMV QIDLPIKRYR EYELVTPVST NLEGRYLSHT 
LSASHKKRSA RDVSSNPEQL FFNITAFGKD FHLRLKPNTQ LVAPGAVVEW HETSLVPGNI 
TDPINNHQPG SATYRIRRTE PLQTNCAYVG DIVDIPGTSV AISNCDGLAG MIKSDNEEYF 
IEPLERGKQM EEEKGRIHVV YKRSAVEQAP IDMSKDFHYR ESDLEGLDDL GTVYGNIHQQ 
LNETMRRRRH AGENDYNIEV LLGVDDSVVR FHGKEHVQNY LLTLMNIVNE IYHDESLGVH 
INVVLVRMIM LGYAKSISLI ERGNPSRSLE NVCRWASQQQ RSDLNHSEHH DHAIFLTRQD 
FGPAGMQGYA PVTGMCHPVR SCTLNHEDGF SSAFVVAHET GHVLGMEHDG QGNRCGDETA 
MGSVMAPLVQ AAFHRYHWSR CSGQELKRYI HSYDCLLDDP FDHDWPKLPE LPGINYSMDE 
QCRFDFGVGY KMCTAFRTFD PCKQLWCSHP DNPYFCKTKK GPPLDGTECA AGKWCYKGHC 
MWKNANQQKQ DGNWGSWTKF GSCSRTCGTG VRFRTRQCNN PMPINGGQDC PGVNFEYQLC 
NTEECQKHFE DFRAQQCQQR NSHFEYQNTK HHWLPYEHPD PKKRCHLYCQ SKETGDVAYM 
KQLVHDGTHC SYKDPYSICV RGECVKVGCD KEIGSNKVED KCGVCGGDNS HCRTVKGTFT 
RTPRKLGYLK MFDIPPGARH VLIQEDEASP HILAIKNQAT GHYILNGKGE EAKSRTFIDL 
GVEWDYNIED DIESLHTDGP LHDPVIVLII PQENDTRSSL TYKYIIHEDS VPTINSNNVI 
QEELDTFEWA LKSWSQCSKP CGGGFQYTKY GCRRKSDNKM VHRSFCEANK KPKPIRRMCN 
IQECTHPLWV AEEWEHCTKT CGSSGYQLRT VRCLQPLLDG TNRSVHSKYC MGDRPESRRP 
CNRVPCPAQW KTGPWSECSV TCGEGTEVRQ VLCRAGDHCD GEKPESVRAC QLPPCNDEPC 
LGDKSIFCQM EVLARYCSIP GYNKLCCESC SKRSSTLPPP YLLEAAETHD DVISNPSDLP 
RSLVMPTSLV PYHSETPAKK MSLSSISSVG GPNAYAAFRP NSKPDGANLR QRSAQQAGSK 
TVRLVTVPSS PPTKRVHLSS ASQMAAASFF AASDSIGASS QARTSKKDGK IIDNRRPTRS 
STLER

Genular Protein ID: 3735925761

Symbol: B7Z2U9_HUMAN

Name: N/A

UniProtKB Accession Codes:

B7Z2U9

Database IDs:

ARBA 1 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 1 InterPro 1 KEGG 1 MEROPS 1 NCBI Taxonomy 1 OrthoDB 1 PeptideAtlas 1 Pfam 2 RefSeq 1

Sequence Information:

  • Length: 161
  • Mass: 17962
  • Checksum: AEE9CF31ED19B0D2
  • Sequence:
    • MVQIDLPIKR YREYELVTPV STNLEGRYLS HTLSASHKKR SARDVSSNPE QLFFNITAFG 
KDFHLRLKPN TQLVAPGAVV EWHETSLVPG NITDPINNHQ PGSATYRIRR TEPLQTNCAY 
VGDIVDIPGT SVAISNCDGL NSVITPVRHS SHMEKQVLEI S

Genular Protein ID: 1589563030

Symbol: Q96AY5_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q96AY5

Database IDs:

ARBA 3 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 GO 5 Gene3D 1 InterPro 4 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 3 PeptideAtlas 1 Pfam 1 RefSeq 1 SAM 1 SMART 1 SUPFAM 1

Citations:

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

Sequence Information:

  • Length: 364
  • Mass: 40211
  • Checksum: A3D54D967D67FD30
  • Sequence:
    • EELDTFEWAL KSWSQCSKPC GGGFQYTKYG CRRKSDNKMV HRSFCEANKK PKPIRRMCNI 
QECTHPLWVA EEWEHCTKTC GSSGYQLRTV RCLQPLLDGT NRSVHSKYCM GDRPESRRPC 
NRVPCPAQWK TGPWSECSVT CGEGTEVRQV LCRAGDHCDG EKPESVRACQ LPPCNDEPCL 
GDKSIFCQME VLARYCSIPG YNKLCCESCS KRSSTLPPPY LLEAAETHDD VISNPSDLPR 
SLVMPTSLVP YHSETPAKKM SLSSISSVGG PNAYAAFRPN SKPDGANLRQ RSAQQAGSKT 
VRLVTVPSSP PTKRVHLSSA SQMAAASFFA ASDSIGASSQ ARTSKKDGKI IDNRRPTRSS 
TLER